A hematology research training program center on red cell diseases has existed at Einstein since 1956, first headed by Helen Ranney, then Ernst Jaffe and during the last 15 years by Ronald L. Nagel, M.D. It presently resides in the Division of Hematology that includes three hospitals and two campuses (East Campus: the Medical School, Jacobi Medical Center and the Weiler Hospital; West Campus: the Monteflore Medical Center). The Program Director (PD) is Head of this Division. The proposal involves senior faculty members with significant experience in research and teaching. Albert Einstein has excellent physical facilities for implementing the program, both at the Division level as well as Institutional common research facilities. The objective of this Program is to train four MDs and/or PhDs annually in the areas of hemoglobin and red cell research, including molecular biology. This training program will recruit much needed investigators to the areas of red cell genetic defects, sickle cell anemia and globin gene regulation. The Program Director has extensive experience in conducting this program and has an active research program of his own involving hemoglobinopathies and red cell aspects of malaria. Other senior faculty members are Joel Friedman, PhD an expert on state-of-the-art hemoglobin spectroscopy, Seetharama Acharya, PhD a protein chemist who is doing ground-breaking work in semisynthesis of polypeptide chains to produce muteins. Mary E. Fabry, PhD, a biophysicist, whose MRI and ion transport expertise is brought to bear on the characterization of abnormal red cells and transgenic animals; DK Kaul, PhD a microcirculatory physiologist interested in the rheological, cellular and molecular basis of vasoocclusion in sickle cell anemia and P. falciparum malaria. The Junior mentors are HM Tsai, MD, an alumni of the Program, who works in the biochemistry of von Willebrand polymers and the pathogenesis of TTP and has produced a paradigm shift in the field, and Eric Bouhassira, PhD, also an alumni of this training program, who has developed novel techniques for the use of CRE/LOX technology to insert DNA constructs in defined sites to study and measure position effects for globin gene expression. The trainers are well funded and are accustomed to interacting with each other, as their CVs attest, which strengthens the program considerably by making it an effort based on teamwork. Trainees will be exposed to more than one senior faculty member. In summary, this research group has a strong training record, a long history of mutual interactions, and is devoted to "orphan maladies".